Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy (of current clinical diagnostic work-up and emerging biomarkers in Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and Cerebrospinal Fluid (CSF), 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model.

Methods/design: In a cohort design 200 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life data, costs and emerging biomarkers are gathered.

Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to the reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period.

A decision analytic model is build combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers.

Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems.

Diagnostic test accuracy (in terms of sensitivity and specificity) of three MRI markers (Whole brain and hippocampal volume, white matter integrity, and functional connectivity) is determined by relating the particular marker to a reference diagnosis. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period.

Change in cognition at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]

Measured by the Mini-mental state examination (MMSE).

Change in dementia severity at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]

Measured by the clinical dementia rating (CDR) scale.

Change in quality of life at 2 years [ Time Frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]

Measured by the Euro-Qol-5D both by the patient and caregiver and measured by the Quality of life Alzheimer's disease state (QoL-AD) both by the patient and caregiver.

By means of questionnaires the health care resource usage is measured by the Resource Utilization in Dementia-questionnaire (RUD-lite) over a period of 2 years using 4 measurement moments to interpolate the data.

Change in productivity at 2 years [ Time Frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]

Work status, income, and productivity losses of both the patient and caregiver are assessed by the adjusted PRODISQ (PROductivity and DISease Questionnaire). The consequences of informal caregiving on paid or unpaid work are assessed by the Health and Labour Questionnaire.

Diagnostic test accuracy (in terms of sensitivity and specificity) of three CSF markers (CSF total tau, CSF phosphorylated tau, and CSF Aβ1-42) is determined by relating the particular marker to a reference diagnosis. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period.

Secondary Outcome Measures:

Demographic changes at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]

Course of cognitive symptoms, Civil status, and Living situation are assessed.

General clinical changes at 2 years [ Time Frame: baseline, 1 year follow up, 2 year follow up ] [ Designated as safety issue: No ]

all new consecutive patients of the participating memory clinics who are suspected of having a primary neurodegenerative disease, meaning that all patients with subjective as well as objective memory complaints are included

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Sampling Method:

Non-Probability Sample

Study Population

200 consecutive patients, of four academic memory clinics specialized in the diagnosis and treatment of memory disorders, who were suspected of having a primary neurodegenerative disease were approached for participating in the study. This included all patients with subjective and/or objective memory complaints. Eligibility criteria were chosen to represent current clinical situation and enable generalisability to clinical practice.

Criteria

Inclusion Criteria:

All new consecutive patients of the participating memory clinics who are suspected of having a primary neurodegenerative disease. This means all patients with subjective and/or objective memory complaints.

CDR 0, 0.5 or 1

MMSE score must be 20 or higher.

Availability of a reliable informer or proxy (who visits or contacts the patient at least once a week).

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01450891